The question today is whether we should use the techniques of gene drive and CRISPR to alter natural populations. There are several risks that must be taken into account: the off-target effects, spread of genetic modifications and imbalance of ecosystems.

What is Gene Drive?

Gene drive consists of directing the biased inheritance of particular genes to alter entire populations. It mainly involves propagating a trait that is harmful for the species, for example a distorted sex ratio, reduced fertility or chemical sensitivity. During normal sexual reproduction, each of the two versions of a given gene have a 50% probability of being inherited. Gene drives are genetic systems that circumvent these traditional rules, hugely increasing the likelihood that the desired gene is transmitted to the offspring. This allows them to spread to all members of a population, even if they reduce the possibility that each individual organism will reproduce. This technique therefore constitutes a tool for curbing the transmission of insect-borne diseases, controlling the spread of invasive species or eliminating herbicide or pesticide resistance.

Gene Drive and CRISP-Cas9

Gene drive occurs in nature, but the idea of using gene drives to control populations of disease-carrying insects was first presented in the 1940s. Then, in 2003, Professor Austin Burt of Imperial College London proposed a new type of gene drive, based on the use of genes that give rise to enzymes that cut the genome of organisms at desired sites (endonucleases). This concept of gene drive is where the use of CRISPR-Cas9 comes in. CRISPR-Cas9 is a new gene editing technique that allows changes to be introduced in the genome efficiently, simply and very inexpensively (Click HERE to read an article on this technique). The combination of both techniques will allow almost any gene in any sexually-reproducing species to be altered, spreading the alterations produced through wild populations.

Implications

Although the debate on gene drive centred for some time on whether it was really possible for scientists to use artificial gene drives for the abovementioned applications, the emergence of CRISPR-Cas9 has meant that this prospect is no longer in doubt. The question today is whether we should use this technique to alter natural populations. There are several risks that must be taken into account: the off-target effects, spread of genetic modifications and imbalance of ecosystems.

First of all, the specificity of the gene drive must be tested, and the off-target effects considered. Any evidence of off-target effects represents a risk for its use. Since the gene drive continues to be fully functional in the mutated strain after it is created, the possibility of off-target mutations also remains, increasing with every generation. If there is any risk of gene flow between the target species and other species, then there is also a risk that the modified sequences could be transmitted, manifesting the negative trait in non-target organisms. It is therefore necessary to have a solid understanding of the gene flow networks related with the target species, and to fully understand the possible specificity limitations.

This technology could become a global threat for the conservation of species

Secondly, high dispersal capacity is a common trait for many invasive species, and the risk of long-distance dispersal is particularly high for species associated with human movement and trade. The spread of a harmful trait depends mainly in the capacity for dispersal of the target species. The dispersal of these traits through other populations would be extremely difficult to detect, reducing the ability and increasing the cost of biosecurity measures to prevent the spread of gene drives to unwanted areas.

Finally, the alteration of an entire population, or its complete eradication, could have drastic and unknown consequences for the ecosystem. The eradication of species could produce unwanted cascades that could represent a greater threat than that of the target species. For example, it could mean that other plagues emerge, or it could affect predators further up the food chain. Taking into account these problems, a regulated cost-benefit-risk analysis might be a prudent step forward.

There may be situations in which the risks identified above are minimal and the use of this technology for controlling invasive species is considered acceptable after a complete cost-benefit-risk analysis, while in many other cases the risks could be considered insurmountable.

Independently of how these biosecurity risks are perceived, without a regulatory framework that provides a mechanism to control these risks with clarity and transparency, this technology could become a global threat for the conservation of species. It is therefore urgent to establish regulations that regulate the biosecurity protocols to comply with, both in the laboratory and in field-scale trials.